898 research outputs found

    Electrorepulsive actuator

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    The invention is a linear actuator that operates under the principle that like charges repel and opposite charges attract. The linear actuator consists of first and second pairs of spaced opposed conductors where one member of each pair of conductors is attached to a fixed member, and where the other member of each pair of conductors is attached to a movable member such as an elongated rod. The two pairs of spaced conductors may be provided in the form of two spacedly interwound helical vanes where the conductors are located on the opposite sides of the two helical vanes. One helical vane extends inwardly from a housing and the other helical vane extends outwardly from an elongated rod. The elongated rod may be caused to move linearly with respect to the housing by applying appropriate charges of like or opposite polarity to the electrical conductors on the helical vanes

    Aniline and methanol toxicity after shoe dye ingestion.

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    A 39-year-old woman intentionally ingested Amberes shoe dye containing both methanol and aniline. She subsequently developed life-threatening methanol poisoning, methemoglobinemia, hemolytic anemia, and sulfhemoglobinemia. Treatment involved methylene blue infusion, emergent hemodialysis, fomepizole therapy, and blood products. Multiple toxicities can occur after ingestion of shoe dyes

    The effect of cyclosporine A on survival time in salicylate-poisoned rats.

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    Salicylate (SAL) produces mitochondrial membrane permeability transition (MPT) with resultant oxidative phosphorylation uncoupling. Cyclosporine A (CSA) inhibits SAL-induced MPT. This study determined if CSA pretreatment prolonged survival time in SAL-poisoned rats. Twenty-nine rats were randomized to receive pre-treatment with either 30 mg/kg CSA or equal volume of control diluent intraperitoneally (i.p.). Four hours later, all rats received 1700 mg/kg sodium salicylate i.p. Survival time, whole blood CSA ([CSA]), and serum sodium ([Na]), glucose and SAL ([SAL]) concentrations were determined. The results showed median survival time for controls was 18 min (95% CI 14-22 min) and for CSA animals was 14 min (95% CI 13-15 min). Univariate and multivariate analyses and Cox proportional hazard regression revealed CSA treatment was associated with higher [SAL], which was associated with shortened survival times. The CSA group also demonstrated shorter survival times for a given [SAL]. In conclusion, CSA pre-treatment shortened survival in SAL-poisoned rats

    The effect of single-dose tramadol on oxycodone clearance.

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    We have noticed increased prescribing of tramadol by emergency physicians for breakthrough pain in patients chronically taking oxycodone. Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism. A randomized controlled trial in 10 human volunteers was performed to determine if single-dose tramadol therapy would impair oxycodone clearance. Subjects were randomized whether to enter the control or experimental arm of the study first, with each subject serving as his or her own control. In the control arm, each subject received 10 mg immediate-release oxycodone orally and had serial plasma oxycodone and oxymorphone concentrations measured over 8 h. The experimental arm was identical except that 100 mg tramadol was ingested 1.5 h before oxycodone. Clearance divided by fraction absorbed (CL/f) was calculated using the dose and the area under the 8-h time-plasma oxycodone concentration curve. Peak plasma oxycodone concentrations (C(max)) and time until peak oxycodone concentrations (T(max)) were secondary outcome parameters. Group size was chosen to produce a power of 0.8 to detect a 20% difference in CL/f between study arms. Values for CL/f, C(max), and T(max) were compared between study arms using two-tailed, paired t-tests. No statistically significant difference between groups was demonstrated for any parameter. We failed to demonstrate that single doses of tramadol impaired oxycodone clearance

    The Pentameric Vertex Proteins Are Necessary for the Icosahedral Carboxysome Shell to Function as a CO\u3csub\u3e2\u3c/sub\u3e Leakage Barrier

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    Background Carboxysomes are polyhedral protein microcompartments found in many autotrophic bacteria; they encapsulate the CO2 fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) within a thin protein shell and provide an environment that enhances the catalytic capabilities of the enzyme. Two types of shell protein constituents are common to carboxysomes and related microcompartments of heterotrophic bacteria, and the genes for these proteins are found in a large variety of bacteria. Methodology/Principal Findings We have created a Halothiobacillus neapolitanus knockout mutant that does not produce the two paralogous CsoS4 proteins thought to occupy the vertices of the icosahedral carboxysomes and related microcompartments. Biochemical and ultrastructural analyses indicated that the mutant predominantly forms carboxysomes of normal appearance, in addition to some elongated microcompartments. Despite their normal shape, purified mutant carboxysomes are functionally impaired, although the activities of the encapsulated enzymes are not negatively affected. Conclusions/Significance In the absence of the CsoS4 proteins the carboxysome shell loses its limited permeability to CO2 and is no longer able to provide the catalytic advantage RubisCO derives from microcompartmentalization. This study presents direct evidence that the diffusion barrier property of the carboxysome shell contributes significantly to the biological function of the carboxysome

    Initial postmarketing experience with crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation.

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    STUDY OBJECTIVE: We describe our postmarketing experience with patients receiving Crotalidae polyvalent immune Fab (CroFab; FabAV) antivenom for treatment of rattlesnake envenomation. METHODS: The charts of 28 patients admitted between March 1 and September 9, 2001, with rattlesnake envenomation and treated with FabAV were reviewed for demographic information, time until antivenom treatment, laboratory findings, evidence of hypersensitivity reaction, length of hospital stay, and readmission to the hospital. RESULTS: All patients had swelling, 20 patients had elevated prothrombin times (\u3e14 seconds), 12 patients had low fibrinogen levels (/dL), and 6 patients had thrombocytopenia (platelet count \u3c120,000/mm(3)) on presentation. The total dose of FabAV ranged from 10 to 47 vials per patient. Hypofibrinogenemia was resistant to FabAV in some patients. On follow-up, recurrence of coagulopathy was detected in 3 patients, and recurrence of thrombocytopenia was detected in 1 patient. Two patients demonstrated delayed-onset severe thrombocytopenia. Recurrence or delayed-onset toxicity might have been underestimated because of incomplete follow-up in some patients. No acute hypersensitivity reactions occurred. Two patients reported mild symptoms of possible serum sickness on follow-up. CONCLUSION: FabAV effectively controlled the effects of envenomation; however, initial control of coagulopathy was difficult to achieve in some cases, and recurrence or delayed-onset hematotoxicity was common. When initially managing hematotoxicity, a trend toward normalization of laboratory values might be a more reasonable end point for FabAV treatment than attainment of normal reference values in nonbleeding patients

    The Pentameric Vertex Proteins Are Necessary for the Icosahedral Carboxysome Shell to Function as a CO2 Leakage Barrier

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    BACKGROUND: Carboxysomes are polyhedral protein microcompartments found in many autotrophic bacteria; they encapsulate the CO(2) fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) within a thin protein shell and provide an environment that enhances the catalytic capabilities of the enzyme. Two types of shell protein constituents are common to carboxysomes and related microcompartments of heterotrophic bacteria, and the genes for these proteins are found in a large variety of bacteria. METHODOLOGY/PRINCIPAL FINDINGS: We have created a Halothiobacillus neapolitanus knockout mutant that does not produce the two paralogous CsoS4 proteins thought to occupy the vertices of the icosahedral carboxysomes and related microcompartments. Biochemical and ultrastructural analyses indicated that the mutant predominantly forms carboxysomes of normal appearance, in addition to some elongated microcompartments. Despite their normal shape, purified mutant carboxysomes are functionally impaired, although the activities of the encapsulated enzymes are not negatively affected. CONCLUSIONS/SIGNIFICANCE: In the absence of the CsoS4 proteins the carboxysome shell loses its limited permeability to CO(2) and is no longer able to provide the catalytic advantage RubisCO derives from microcompartmentalization. This study presents direct evidence that the diffusion barrier property of the carboxysome shell contributes significantly to the biological function of the carboxysome

    110 Years of Avipoxvirus in the Galapagos Islands

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    The role of disease in regulating populations is controversial, partly owing to the absence of good disease records in historic wildlife populations. We examined birds collected in the Galapagos Islands between 1891 and 1906 that are currently held at the California Academy of Sciences and the Zoologisches Staatssammlung Muenchen, including 3973 specimens representing species from two well-studied families of endemic passerine birds: finches and mockingbirds. Beginning with samples collected in 1899, we observed cutaneous lesions consistent with Avipoxvirus on 226 (6.3%) specimens. Histopathology and viral genotyping of 59 candidate tissue samples from six islands showed that 21 (35.6%) were positive for Avipoxvirus, while alternative diagnoses for some of those testing negative by both methods were feather follicle cysts, non-specific dermatitis, or post mortem fungal colonization. Positive specimens were significantly nonrandomly distributed among islands both for mockingbirds (San Cristobal vs. Espanola, Santa Fe and Santa Cruz) and for finches (San Cristobal and Isabela vs. Santa Cruz and Floreana), and overall highly significantly distributed toward islands that were inhabited by humans (San Cristobal, Isabela, Floreana) vs. uninhabited at the time of collection (Santa Cruz, Santa Fe, Espanola), with only one positive individual on an uninhabited island. Eleven of the positive specimens sequenced successfully were identical at four diagnostic sites to the two canarypox variants previously described in contemporary Galapagos passerines. We conclude that this virus was introduced late in 1890â€Čs and was dispersed among islands by a variety of mechanisms, including regular human movements among colonized islands. At present, this disease represents an ongoing threat to the birds on the Galapagos Islands

    Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

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    Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management

    Combining biomarker and bulk compositional gradient analysis to assess reservoir connectivity

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    Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Organic Geochemistry 41 (2010): 812-821, doi:10.1016/j.orggeochem.2010.05.003.Hydraulic connectivity of petroleum reservoirs represents one of the biggest uncertainties for both oil production and petroleum system studies. Here, a geochemical analysis involving bulk and detailed measures of crude oil composition is shown to constrain connectivity more tightly than is possible with conventional methods. Three crude oils collected from different depths in a single well exhibit large gradients in viscosity, density, and asphaltene content. Crude oil samples are collected with a wireline sampling tool providing samples from well‐defined locations and relatively free of contamination by drilling fluids; the known provenance of these samples minimizes uncertainties in the subsequent analysis. The detailed chemical composition of almost the entire crude oil is determined by use of comprehensive two‐dimensional gas chromatography (GC×GC) to interrogate the nonpolar fraction and negative ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT‐ICR MS) to interrogate the polar fraction. The simultaneous presence of 25‐ norhopanes and mildly altered normal and isoprenoid alkanes is detected, suggesting that the reservoir has experienced multiple charges and contains a mixture of oils biodegraded to different extents. The gradient in asphaltene concentration is explained by an equilibrium model considering only gravitational segregation of asphaltene nanoaggregates; this grading can be responsible for the observed variation in viscosity. Combining these analyses yields a consistent picture of a connected reservoir in which the observed viscosity variation originates from gravitational segregation of asphaltene nanoaggregates in a crude oil with high asphaltene concentration resulting from multiple charges, including one charge that suffered severe biodegradation. Observation of these gradients having appropriate magnitudes suggests good reservoir connectivity with greater confidence than is possible with traditional techniques alone.The mass spectrometry work was supported by the NSF Division of Materials Research through DMR‐06‐54118, and the State of Florida
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